Clinical experts with the Quebec government say there isn’t enough evidence yet for them to recommend widespread use of colchicine to treat COVID-19 patients, dampening hopes the drug could be a short-term tool to reduce hospitalizations and deaths.
Last month, the Montreal Heart Institute released a statement vaunting the results of a clinical trial that found the rate of hospitalization or death was 21 per cent lower among patients who took colchicine, compared to a placebo. It reported even more impressive results among “patients with a proven diagnosis.”
The findings made headlines around the world. Premier François Legault called the results “big news.”
Colchicine is a cheap, widely available drug in Canada, well-known to doctors for its effectiveness at treating gout. And so far physicians have struggled to find effective drug treatments for the new disease.
The news release, though, left out key elements of the study. When the researchers released more detailed findings, their peers in the medical community struck a more cautious tone.
McGill’s Office for Science and Society joined several others in decrying a practise known as “science by press release,” where seemingly exciting findings are published by funding bodies before being peer-reviewed and with little in the way of data.
Amid the controversy, the Quebec provincial government’s clinical research institute (known by its French initials as the INESSS) quickly undertook its own detailed analysis of the colchicine study.
In a briefing Thursday with journalists, the INESSS experts said based on the available evidence they consider it “premature to support the use of colchicine in non-hospitalized persons with a diagnosis of COVID-19.”
Finding inconclusive, INESSS says
The $ 14-million colchicine study, funded in part by the Quebec government, was launched in March, initially with the aim of recruiting 6,000 people in six different countries.
Led by Dr. Jean-Claude Tardif, director of the Montreal Heart Institute’s research centre, the investigators wanted to see whether the anti-inflammatory medication would limit symptoms of the disease in people with pre-existing medical conditions.
But the study was halted after recruiting 4,500 participants. The researchers cited both logistical issues and the desire to get results to health-care professionals as quickly as possible, given the strain the pandemic was placing on hospital resources.
In its review, the INESSS said that was the right decision given the circumstances, and acknowledged Tardif’s hypothesis and research design were sound.
Dr. Luc Boileau, the president of the advisory body, said the move to publish the results in a press release, ahead of peer-review, was “not irresponsible but is infrequent.”
“We’re in the context of a pandemic … and there is a legitimate public interest in the results,” he said.
But following a close reading of those results, the advisory body determined there was insufficient evidence to draw firm conclusions about the benefits of colchicine for COVID-19 patients.
The participants in the study included patients who tested positive via the gold-standard PCR test, as well as those who had been diagnosed simply by virtue of having been exposed to someone with the virus (known as an epidemiological link).
When those two groups were considered together, there was no statistically significant difference in hospitalizations or deaths between participants receiving colchicine and those receiving a placebo, said Dr. Michèle de Guise, who headed the review.
There was a statistically significant difference among those who tested positive through PCR. In this smaller group, those who received the drug were 25 per cent less likely to die or require hospitalizations when compared with the placebo group.
That was one of the findings that went into the news release put out by the Montreal Heart Institute. But when considered in absolute terms, the difference is less impressive.
In the placebo group, six per cent of the 2,084 subjects either died or required hospitalization. In the experimental group, 4.6 per cent of 2,075 subjects died or required hospitalization.
From a clinical perspective, that 1.4 percentage point difference “means that 71 patients would need to be treated with colchicine to achieve one less event,” said de Guise.
Potentially alarming side effect
The study also turned up a potentially frightening side-effect. Eleven participants who took colchicine experienced a pulmonary embolism, compared with two in the placebo group.
That alarmed the experts INESSS consulted, de Guise said.
“That was unexpected and it worried them,” she added.
The INESSS stressed its findings were preliminary and said it would review them as more data becomes available.
In the meantime, COVID-19 patients interested in using the drug should have a discussion with their physician, said Boileau.
Quebec’s Health Ministry said it would issue guidelines on colchicine treatments for COVID-19 after taking the time to analyze the recommendations made by the INESSS.
A spokesperson for the Montreal Heart Institute said Thursday they too would read the INESSS report before commenting.